The objectives of this project are to define the epidemiology, risk factors, transmission kinetics and pathogenesis of chlamydial infections in different population settings and different disease states using new molecular amplification techniques To address these objectives, we implemented non-invasive screening with molecular assays for C. trachomatis genital tract infections and documented extremely high rates of infection (31%) in sexually active female adolescents. The median time to repeat infection was seven months, resulting in new recommendations to the PHS for routine screening of all sexually active adolescent females every six months for this common infection. In addition, we implemented a screening program of 20,000 female military recruits from 50 states and documented a prevalence of 9.2% among these women. In a preliminary study, we screened 3,000 male recruits, of whom 5.3% were infected and 86% of those infected were without any genital symptoms. We completed two mass antibiotic treatment trials aimed at lowering the prevalence and incidence of chlamydial genital and ocular infections respectively. Marked reductions in chlamydial infections were documented with subsequent control and prevention of blinding trachoma, which led to a combined WHO control program utilizing mass treatment with azithromycin. Of increasing importance to this laboratory is the investigation of the role of Chlamydia pneumoniae in the development of atherosclerosis utilizing seroepidemiologic, pathologic, and animal models to address this issue. We have found evidence of C. pneumoniae infection in 50% of coronary and carotid atheromas by immunocytochemistry and/or PCR. We isolated C. pneumoniae from a heart transplant patient and demonstrated in vitro that C. pneumoniae can infect and proliferate in coronary artery endothelial cells and aortic artery smooth muscle cells. In a preliminary animal model study, we were able to accelerate atheroscerotic lesions of the aorta with C. pneumoniae infection in apoE-deficient mice at a greater rate than non-infected control mice. Co-infection with cytomegalovirus also appeared to further potentiate the atherosclerotic process.